The aforementioned two classes of drugs are the only that are intrinsically euphoric - mind-set and setting independent - euphoriants due to their dopaminergic actions at the nucleus accumbens shell. They are pharmacologically euphorigenic; the outcome and effects of using them does not depend on the personality, mind-set, or setting of the user.

Other drugs can be euphoriants, dependent on the personality, mind-set, and setting of the person using them. Some classes of these drugs are:

Deliriants[3] - This class is primarily represented by anticholinergic drugs, of which first-generation anti-histamines are prototypical. Others include orphenadrine, scopolamine, diphenhydramine, and atropine. Their euphoric effects are fairly mild and unpredictable in different people, some being more susceptible than others, therefore overall having a low potential for abuse.

The effects of hallucinogens can be euphoric in some people, in some situations, but typically are mood-neutral (cf. bad trip), generally amplifying the emotions of the user.[4] Whereas an opioid will still be euphoric in a depressed person, or a depressant an anxiolytic in an anxious person, a hallucinogenic drug will usually increase the intensity of the depression, or increase the sharpness of anxiety by orders of magnitude (hallucinogens are anxiogenic even in non-anxious individuals[4]). Hallucinogens will, likewise, increase the intensity of mild happiness or euphoria exponentially. The effects of hallucinogens are drastically different in different people, and even in the same person on two different occasions[4], especially with a different mind-set or in different situations. Having a good mindset and physical setting are absolutely necessary to have a good experience using a hallucinogen. Mentally ill people, especially people with schizophrenia or anxiety disorders, usually have a negative reaction to hallucinogens.[4] People with a family history of mental illness have a higher than normal chance of adverse reaction.[4]

Many euphoriants have a "mixed mechanism of action", which is to say they don't categorize neatly in to one of the above groups, or affect more than one system of receptors or neurotransmitters. Some drugs have a predominant mechanism of action at certain doses, and another mechanism of action becomes predominant at higher doses. Some drugs have a mixed mechanism of action at all doses, and some drugs have vastly different mechanisms of action depending on the stereoisomer used.

Cocaine has a tendency to induce psychosis and seizures in high doses, likely linked to its agonism of the sigma receptor, which is minor with moderate dosage.

Methadone, being a potent mu-opioid agonist in lævo-rotatory form and NMDA-antagonist in dextro-rotatory form. The only commercially available preparations are the racemate, so the drug has, in effect, a mixed mechanism of action, even though one specific stereoisomer of the drug is responsible for each unique pharmacological action. Its effects are mostly that of an opioid, with some dissociative effects from NMDA-antagonism based on the dosage.

Methorphan is another similar example - dextromethorphan, used in over-the-counter cough preparations, is a dissociative NMDA-antagonist in high dosages, with a degree of sigma-receptor agonism, increasing with dosage. Levomethorphan is a potent mu-opioid analgesic. The racemate - methorphan - has a spectrum of effects based on its mechanisms of action.

Pentazocine is a mixed-opioid receptor agonist, and sigma receptor agonist. In low doses, it causes effects similar to that of low-dose morphine - in higher doses, dissociation, hallucinations, and delirium are common, as the effects upon kappa opioid receptors and the sigma receptor become more prominent.

Dimethyltryptamine (DMT), a naturally-occurring hallucinogen produced by many plants and found in trace amounts in the mammalian brain, has effects on both the serotonin receptors and the sigma receptor, causing a combination of psychedelic and dissociative effects.